{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:18:52Z","timestamp":1783448332276,"version":"3.55.0"},"reference-count":5,"publisher":"Bioscientifica","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":207,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:p>Autoimmune hypothyroidism occurs rarely before 3 years of age. Two siblings were diagnosed with autoimmune hypothyroidism at age 5 and 16 months, presenting with classic symptoms of hypothyroidism, abnormal thyroid function tests (TSH: 200 and 660 mU\/L; reference range (RR): 0.73\u20138.4 mU\/L; Free T4: 5.9 and &amp;lt;1.3 pmol\/L; RR: 11.9\u201325.6 pmol\/L), and high thyroid peroxidase antibody levels. Thyroxine medication alleviated their symptoms. Apart from mild infections, the siblings exhibited no other major disorders. Whole exome sequencing identified a pathogenic STAT3 gain-of-function variant, most commonly associated with infantile-onset multi-organ autoimmune disorder. Genetic testing for early-onset hypothyroidism may reveal specific etiologies, impacting follow-up and treatment.<\/jats:p>","DOI":"10.1530\/etj-25-0260","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T11:39:24Z","timestamp":1763638764000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":0,"title":["Very-early-onset autoimmune hypothyroidism: a report of two cases with STAT3 gain-of-function variant"],"prefix":"10.1530","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7994-8547","authenticated-orcid":true,"given":"Rowmika","family":"Ravi","sequence":"first","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Niskanen","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Pat","family":"Reeve","sequence":"additional","affiliation":[{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiina","family":"Makkonen","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harri","family":"Niinikoski","sequence":"additional","affiliation":[{"name":"3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorma","family":"Toppari","sequence":"additional","affiliation":[{"name":"3"},{"name":"4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Kero","sequence":"additional","affiliation":[{"name":"1"},{"name":"3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"2026070714003111600_bib1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1056\/NEJM199402173300704","article-title":"Brief report: hypothyroidism caused by chronic autoimmune thyroiditis in very young infants","volume":"330","author":"Foley","year":"1994","journal-title":"N Engl J Med"},{"key":"2026070714003111600_bib2","first-page":"42","article-title":"Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report","volume":"18","author":"Marzuillo","year":"2016","journal-title":"Ital J Pediatr"},{"key":"2026070714003111600_bib3","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.jaip.2019.02.018","article-title":"Clinical aspects of STAT3 gain-of-function germline mutations: a systematic review","volume":"7","author":"Fabre","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2026070714003111600_bib4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ajo.2021.10.025","article-title":"Clinical spectrum and geographic distribution of keratitis fugax hereditaria caused by the pathogenic variant c.61G&gt;C in NLRP3","volume":"236","author":"Immonen","year":"2022","journal-title":"Am J Ophthalmol"},{"key":"2026070714003111600_bib5","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.jaci.2022.09.002","article-title":"Monogenic early-onset lymphoproliferation and autoimmunity: natural history of STAT3 gain-of-function syndrome","volume":"151","author":"Leiding","year":"2023","journal-title":"J Allergy Clin Immunol"}],"container-title":["European Thyroid Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/etj.bioscientifica.com\/view\/journals\/etj\/14\/6\/ETJ-25-0260.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/etj.bioscientifica.com\/downloadpdf\/journals\/etj\/14\/6\/ETJ-25-0260.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-25-0260\/506432\/etj-25-0260.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-25-0260\/506432\/etj-25-0260.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:00:39Z","timestamp":1783447239000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article\/14\/6\/e250260\/75624\/Very-early-onset-autoimmune-hypothyroidism-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":5,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12,1]]}},"URL":"https:\/\/doi.org\/10.1530\/etj-25-0260","relation":{},"ISSN":["2235-0802","2235-0640"],"issn-type":[{"value":"2235-0802","type":"electronic"},{"value":"2235-0640","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"article-number":"e250260"}}